Early chemical events in carcinogenesis by aromatic amines are investigated by the application of whole animal tumor induction experiments, structural studies on adducts of carcinogens and non-carcinogens on target tissue nucleic acids, biochemical and pathological studies on target tissue after short-term administration of carcinogens and non-carcinogens, and theoretical studies on the mechanisms of reaction of a variety of ultimate carcinogens. 2-Acetamidofluorene, 2-acetamidophenanthrene and 4-acetamidobiphenyl are all mammary carcinogens in the female rat, and ear duct gland carcinogens in both males and females. Only acetamidofluorene is a liver carcinogen, however. Previous work in this laboratory and others has shown different levels of binding and activation mechanisms for the three compounds in the male rat liver. The adducts of aminophenanthrene with rat liver nucleic acids must still be determined to achieve relatively complete chemical comparison of the three compounds' binding properties. Short term toxicity of all three compounds will be determined using histological and biochemical (thymidine incorporation) methods. Binding of acetamidofluorene to chromosomal proteins in vivo and in vitro will be determined. In vitro binding will be mediated by N-acetoxy-2-acetamidofluorene, and performed with whole chromatin and separated chromosomal proteins. The ability of 2-acetamidophenanthrene to initiate liver carcinogenesis in a two-stage system will be determined. Joint studies with H.-G. Neumann of the University of Wurzburg will be continued, on determining the nature of in vivo adducts of aminostilbene derivatives. Theoretical studies will be undertaken on the ground state of aryl-and acetylaryl-nitrenium ions, on explaining the difference in solvent competition factors among arene oxides, and on predicting reactions of ultimate carcinogens with nucleic acid bases, using polyelectronic perturbaton theory.